In recent years, using micro-machine technology and microscopic processing technology, systems are developed in which devices and means, for example, pumps, valves, flow channels, sensors and the like for performing conventional sample preparation, chemical analysis, chemical synthesis and the like are miniaturized and integrated on a single chip.
These systems are called μ-TAS (Micro Total Analysis System), bioreactor, lab-on-chips, and biochips, and much is expected of their application in the fields of medical testing and diagnosis, environmental measurement and agricultural manufacturing.
As seen in genetic screening in particular, in the case where complicated steps, skilful operations, and machinery operations are necessary, a microanalysis system, which is automatic, has high speed and is simple, is very beneficial not only in terms of reduction in cost, required amount of sample and required time, but also in terms of the fact that it makes analysis possible in cases where time and place cannot be selected.
At a site where various testing such as clinical testing is carried out, even in a case of measuring with a microreactor of a chip type which can quickly output results regardless of place, quantitation and accuracy in analysis are deemed to be important.
However, it is required to establish a reliable liquid feeding system with a simple structure, since there are severe limitation with respect to size and shape for an analysis chip such as a chip type microreactor. A micro liquid control device that has high accuracy and excellent reliability is needed. The inventors of the present invention have already proposed a suitable micropump system as a micro liquid control device which satisfies this requirement (Patent Document 1: Japanese Patent Application Laid-Open No. 2001-322099 Publication and Patent Document No. 2: Japanese Patent Application Laid-Open No. 2004-108285 Publication).
Furthermore, the inventors of the present invention have already proposed, in Patent Document 3 (Japanese Patent Application 2004-138959), a testing microchip (microreactor) including: a specimen storage section in which specimen is stored; a reagent storage in which reagent is stored; a reaction section which has a reaction flow channel in which the specimen stored in the specimen storage section and the reagent stored in the reagent storage section are merged to perform a predetermined reaction processing; and a testing section which has a testing channel for performing a predetermined test on the reaction-processed substance obtained from the reaction in the reaction section, wherein the specimen storage section, the reagent storage section, the reaction section, and the testing section are connected continuously by a series of flow channels from the upstream side to the downstream side on a single flow channel.
In the microreactor of Patent Document 3 (Japanese Patent Application No. 2004-138959), the flow channels have a number of liquid feed control sections 113 as shown in FIG. 8. This liquid feed control section 113 interrupts the passage of liquid until the feed pressure in the normal direction of flow, which is from upstream to downstream, reaches a predetermined pressure, and permits passage of the liquid by applying a feed pressure that is greater than or equal to the predetermined pressure.
That is to say, each liquid feed control section 113 includes a liquid feed control path (with a smaller flow channel diameter) 151 having a smaller cross-sectional flow area than the flow channels 115, through which the flow channel 115 on the upstream side (hereinafter, also referred to as “the upstream flow channel”) and the flow channel 115 on the downstream side (hereinafter, also referred to as “the downstream flow channel”) communicate with each other. Thus, liquid having reached the liquid feed control channel 151 is restricted from passing from the flow channel 115 on the upstream side to the other side.
Due to surface tension, a predetermined feed pressure is needed in order to expel liquid from the liquid feed control path end 151a which has a small cross-sectional area (small diameter) to the downstream flow channel which has a large cross-sectional area (large diameter). Thus, liquid feed control sections 113 are disposed at predetermined locations on the flow channels of the testing microchip, and by controlling the pump pressure from the micropump that is not shown, passing and stopping of the liquid is controlled.
Thus, it is possible for example to temporarily stop the movement of liquid at a predetermined location on a flow channel, and then resume feeding of the liquid to the downstream flow channel at a predetermined timing. Herein, if the inner surface of the liquid feed control path 151 is formed of a hydrophilic material, it is preferable that the inner surface of the liquid feed control path 151 is coated with a water repellent coating such as a fluorine based coating.
By providing a liquid feed control path 151 which allows an upstream flow channel 115 and a downstream flow channel 115 to communicate with each other and has a smaller cross-sectional flow area than the flow channels, feed timing can be controlled.
[Patent Document 1] Japanese Patent Application Laid-Open No. 2001-322099 Publication
[Patent Document No. 2] Japanese Patent Application Laid-Open No. 2004-108285 Publication
[Patent Document 3] Japanese Patent Application No. 2004-138959
[Non-Patent Document 1] “DNA Chip Technology and Applications” “Proteins, Nucleic Acids and Enzymes” Volume 43 Issue 13 (1998) Published by Fusao Kimizuka and Ikunoshin Kato, Kyoritsu Publishing Corp.
In such a known testing microchip, if gas bubbles are present in the liquid, as shown in FIG. 9, gas bubbles K are collected at a liquid flow path entrance 115a that connects an upstream flow channel 115 with a larger diameter and a liquid feed control channel 151 with a smaller diameter, and a liquid flow path entrance 115a is blocked.
Accordingly, a micropump pressure not lower than a set pressure is needed in order to pass liquid from the upstream flow channel 115 with a large diameter, via the liquid feed control path 151 with a small diameter, to the downstream flow channel 115 with a large diameter, and accurate liquid feed control becomes impossible.
Thus, it is possible, for example, that a predetermined testing may not be performed accurately because the specimen and the reagent are not mixed at a suitable time or they are not mixed in a predetermined mixing ratio, resulting in no reaction.
Furthermore, a gas bubble K that blocks the flow path entrance 115a may flow all at once from the upstream channel 115 with a large diameter to the downstream flow channel 115 with a large diameter via the liquid feed control path 151 with a small diameter, and bonding of the reagent, such as a biotin modified chimera primer for specific hybridization of the gene to be an object of detection, and a specimen is inhibited due to the effect of the gas bubbles and the appropriate testing cannot be performed at the testing section.
The present invention was conceived in view of this situation, and the object thereof is to provide a testing microchip and a testing apparatus in which this testing microchip is used. At a liquid feed control section disposed in a flow channel of the testing microchip, gas bubbles which come from an upstream liquid flow channel do not collect at a flow path entrance which leads to a liquid feed control path with a small diameter nor block the flow path entrance; the passage of liquid can be temporarily stopped and then resumed at a predetermined pressure at an appropriate time. It is possible to stop the liquid flow once and pass the liquid at a predetermined pressure and at a suitable timing, while preventing the gas bubbles from passing downstream. Thus, the accuracy of the liquid feed control section is high and accurate testing can be performed with the reliable testing microchip and the testing apparatus using the microchip.